Core Viewpoint - The emergence of GLP-1 receptor agonists, such as Semaglutide developed by Novo Nordisk, marks a new era in safe and effective weight loss, initially intended for type 2 diabetes treatment but showing significant weight reduction effects in non-diabetic patients [2][3]. Group 1: GLP-1 Receptor Agonists - GLP-1 receptor agonists primarily reduce caloric intake, potentially mediated by activating GLP-1 receptors in the central nervous system, leading to significant weight loss [2]. - These drugs are generally considered safe but may cause gastrointestinal side effects, including nausea, vomiting, and diarrhea [2]. - A major challenge with GLP-1 receptor agonists is the difficulty in maintaining weight loss long-term due to metabolic adaptation, which reduces energy expenditure and can lead to weight regain upon discontinuation [2]. Group 2: NN501 Development - A new peptide analog, NN501, developed by researchers from the University of Manchester and Novo Nordisk, shows weight loss effects comparable to Semaglutide but operates through a different mechanism, primarily increasing energy expenditure via sustained fatty acid oxidation rather than reducing food intake [3][5]. - NN501 does not produce significant gastrointestinal side effects or muscle loss, and weight rebound after discontinuation is less pronounced compared to GLP-1 receptor agonists [5][7]. - This new treatment could serve as a viable alternative or complementary therapy for obesity management [7].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 白内障 作为全球排名首位致盲性眼病，患者数量超过 9500 万。随着糖尿病发病率攀升， 糖尿病性白内障 （DC） 的防治压力日益加剧。临床上，糖尿病性白内 障患者手术并发症风险比普通患者高约 30%，但其术前精准诊断却面临两大难题： 诊断滞后 ：依赖患者自述病史或单次血糖检测，易漏诊； 采样困难 ：传统分 子诊断需采集眼内房水等侵入性样本，无法用于术前筛查。 眼泪 是唯一可直接获取的眼部非侵入性体液，但因其微量特性 （单次采集仅微升级别） ，一直难以实现高效代谢分析。 近日， 华东师范大学 万晶晶 教授团队 联合上海交通大学医学院附属第九人民医院 范先群 院士、 苏蕴 副研究员 、 郭涛 主任医师，在 Nature 子刊 Nature Communications 上发表了题为： A mass spectrometry-based strategy allows signature metabolite identification in tear fluid from people with diabetic cataracts 的研究论文。 这项研究颠覆了传统眼科诊 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 哺乳动物的大脑是一个错综复杂的神经元回路网络，由数十亿个神经元通过数以万亿计的突触相互连接而 成。在这个复杂的结构中，单个神经元在形态、转录身份和功能作用方面表现出显著的异质性。揭开大脑 的组织原则和功能连接性需要具备单细胞分辨率的方法学，以捕捉这种多样性。 基因标记、高分辨率成像和计算分析方面的最新进展，极大地促进了在哺乳动物系统中对整个大脑神经元 形态的重建工作。这些进展为了解介观尺度 （即细胞水平） 的连接性和支撑大脑功能的结构模式提供了关 键见解。然而，要想生成具有单神经元分辨率的全面大规模脑图谱，仍需在 标记准确度和成像效率方面取 得进一步创新。 近日，北京生命科学研究所/清华大学生物医学交叉研究院 林睿 实验室与北京脑科学与类脑研究所 罗敏敏 实验室合作，在 Cell 子刊 Neuron 上发表了题为： Ultrabright Chemical Labeling Enables Rapid Neural Connectivity Profiling in Large Tissue Samples 的研究论文，该论文还被选为当期 封面论文 。 该研究提出了一种 ...

Group 1 - The 6th Bio-Manufacturing Industrial Conference will take place on December 2, 2025, at the Guangming Cultural and Art Center in Shenzhen, focusing on synthetic biological manufacturing [2][4][40] - The conference is organized by several prominent institutions, including the Chinese Society of Biotechnology and the Shenzhen Institutes of Advanced Technology [2][39] - The event aims to gather key players from industry, academia, research, and investment sectors to discuss trends and insights in bio-manufacturing [3][45] Group 2 - A second batch of distinguished guests has been announced, featuring experts from various fields who will engage in deep discussions and share valuable insights [3][45] - The conference will include multiple forums and sessions, covering topics such as bio-manufacturing in the Guangdong-Hong Kong-Macao Greater Bay Area, pharmaceuticals, agriculture, and automation [49][50] - Evening sessions will feature project roadshows highlighting emerging forces in the bio-manufacturing industry [50]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肝细胞癌 （HCC） 是 肝癌 的主要亚型，也是全球癌症相关死亡的主要原因之一，其发病率和死亡率一直 居高不下。 肿瘤相关巨噬细胞 （TAM） 在塑造 肝细胞癌 （HCC） 的免疫微环境中发挥着着关键作用， 影响肿瘤进展和免疫治疗反应。 N 7 -甲基鸟苷 （m 7 G） 是一 种常见的 RNA 表观遗传修饰， WDR4 是 m 7 G 甲基转 移酶复合物中的一 种 tRNA 结合辅助因子，但其独立功能仍知之甚少。 在这项最新研究中，研究团队发现， WDR4 在 肝细胞癌 （HCC） 相关的 肿瘤相关巨噬细胞 （TAM） 中 的表达显著上调，并与不良预后相关。 单核细胞来源的巨噬细胞中 WDR4 的缺失 （而不是驻留 Kupffer 细胞 中的 WDR4 缺失） ， 会将肿瘤相关巨噬细胞 （TAM） 编程为抗肿瘤表型，从而抑制肝细胞癌 （HCC） 的进展。 从机制上来说，细胞质中的 WDR4 通过直接与 eIF4E2 相互作用，独立于 m 7 G 修饰来增强 eIF4E 介导 的 ABCA1 的选择性翻译，从而促进膜胆固醇外流并维持促肿瘤极化。利用 CpG-siRNA ...

Core Viewpoint - The study highlights the potential of MHC-II-restricted neoantigen vaccines to enhance T cell infiltration and overcome resistance to immune checkpoint inhibitors (ICIs) in cold tumors, providing a promising new strategy for cancer treatment [3][5]. Group 1: Research Findings - MHC-II-restricted neoantigen vaccines increase T cell infiltration in cold tumors [8]. - The vaccine induces enrichment of the immune checkpoint signaling axis PVR-TIGIT [8]. - The combination of the vaccine with TIGIT blockade enhances anti-tumor effects and delays T cell exhaustion [8]. Group 2: Mechanism of Action - The vaccine utilizes tumor-specific gene mutations to present neoantigens via MHC-II molecules to CD4+ T cells, enhancing anti-tumor immune responses [4]. - The study utilized a melanoma mouse model to evaluate the vaccine's efficacy, analyzing immune responses through flow cytometry and single-cell RNA sequencing [5]. - Results showed that the vaccine promotes inflammatory signaling within the tumor microenvironment, enhancing the infiltration of CD4+ and CD8+ T cells, and increasing interferon (IFN)-γ production [5].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肝细胞癌 （HCC） 是 肝癌 的主要亚型，也是全球癌症相关死亡的主要原因之一，其发病率和死亡率一直 居高不下。 尽管靶向肿瘤特异性抗原已成为癌症免疫治疗的基石，但当前的方法主要聚焦于基因突变产生的新抗原， 其人群覆盖率有限。 2025 年 11 月 28 日，复旦大学附属中山医院 樊嘉 院士、 高强 教授团队在 Cell Research 期刊发表了题 为： Harnessing alternative splicing for off-the-shelf mRNA neoantigen vaccines in hepatocellular carcinoma 的研究论文。 该研究发现， 肝细胞癌 （HCC） 中 mRNA 异常剪接 事件的发生频率远高于体细胞突变，并能产生数量 更多、免疫原性更强且患者适用性更广的 免疫原性多肽 。基于这一发现，研究团队开发了利用 mRNA 异 常剪接的现货型 mRNA 疫苗，用于肝细胞癌治疗。 在这项最新研究中，研究团队通过对 279 例 肝细胞癌 （HCC） 患者的多组学数据进行整合分析，发现 mRNA 异常剪接 事件的发生频率比 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 该研究首次发现，在人类和小鼠的多能干细胞共培养中，通过" 隧道纳米管 " （ Tunneling Nanotube， TNT ） 结构进行的 跨物种 RNA 交换 ， 可激活小鼠细胞的 RNA 先天 免疫通路，进而通过"细胞竞争"清 除人类细胞。 该研究进一步证实 ，敲除通路关键蛋白 MAVS 能够削弱小鼠细胞竞争力，在不修饰人类细胞的情况下，显 著提升人类多能干细胞在小鼠胚胎中的存活率和嵌合率。 这一发现揭示了物种间屏障和细胞竞争的新机 制， 证明了靶向抑制宿主免疫通路是提高动物体内的人类细胞嵌合率的有效策略，为再生医学提供了更具 安全性的"宿主改造"新范式。 利用 人类多能干细胞 （hPSC） 创建 跨物种嵌合体 ， 为模拟人类发育和生成供体器官提供了前景广阔的 策略，然而，人类细胞在其他物种中的整合效率低下，这也成为 创建 跨物种嵌合体面临的 主要障碍。 目前改善人源细胞嵌合率的努力，多集中于对供体 hPSC 进行基因改造，而对宿主进行调控的研究仍然不 足。 2025 年 11 月 24 日，德克萨斯大学西南医学中心 吴军 团队与基因组多维解析技术全国重点实验室/ ...

Core Viewpoint - Functional nucleic acids (FNA) represent a transformative advancement in molecular biology and precision medicine, showcasing their structural diversity and functional potential in various biomedical applications [3][10]. Group 1: Characteristics and Types of FNA - FNA is characterized by unique secondary and tertiary structures formed through the complementary pairing of nucleotide bases, enabling biological functions such as specific target recognition, molecular binding, and catalytic activity [10]. - Aptamers, a type of FNA, are synthetic oligonucleotide sequences known for their high specificity and affinity towards various targets, functioning as "chemical antibodies" [10]. - DNAzymes are catalytically active DNA molecules evolved through in vitro selection, capable of executing specific biochemical reactions such as the cleavage and ligation of RNA and DNA [10]. Group 2: Production and Engineering Strategies - The production methods, structural principles, and biological functions of key FNAs, specifically aptamers and DNAzymes, are crucial for their application in biomedical fields [9][10]. - Engineering strategies to optimize FNA molecular characteristics include enhancing stability, affinity, and catalytic efficiency through rational design and chemical modifications [9][10]. Group 3: Clinical Applications and Challenges - The clinical translation of FNA is progressing, with two aptamer drugs, Macugen and Izervay, already approved for treating age-related macular degeneration, while DNAzymes are currently in clinical trials [10]. - Challenges remain in the clinical application of FNA, including issues related to nucleic acid degradation, delivery efficiency, and regulatory complexities [10].

Core Viewpoint - The article discusses the development and potential of the Fanzor system, a compact RNA-guided DNA nuclease, for precise genome editing in eukaryotic cells, highlighting its advantages over traditional Cas9 systems and its application in disease treatment [3][9]. Group 1: Fanzor System Overview - Fanzor is a newly discovered CRISPR-like system that allows for precise genome editing in eukaryotic organisms, with a compact size of 400-700 amino acids, making it suitable for delivery via a single AAV vector [3][9]. - The traditional AAV delivery system has a maximum packaging capacity of 4.7 kb, which is insufficient for larger Cas proteins like SpCas9 and AsCas12a, necessitating the use of dual AAV vectors [3]. Group 2: Research Developments - A study published by a team from Fudan University introduced an engineered hypercompact Fanzor-ωRNA system, which demonstrated enhanced genome editing activity, achieving efficiency improvements of 6-129 times compared to previous versions [4][11]. - The engineered SpuFz1 V4 system, derived from soil fungus, showed strong genome editing capabilities in human cells, marking it as the most active member of the Fanzor family [9][11]. Group 3: Applications and Potential - The compact structure of SpuFz1 V4 allows for effective in vivo delivery using a single AAV, enabling robust genome editing in animal models, such as efficient editing of the Nfkb1 gene in mouse retinas [10][11]. - The research indicates that the Fanzor platform can be developed into base editors, facilitating efficient single-base editing, which has significant implications for genetic research and therapeutic applications [5][9].